tbuckley/cabot-search huggingface dataset:
Myocardial DNA Damage Predicts Heart Failure Outcome in Various Underlying Diseases
Authors: Zhehao Dai, Toshiyuki Ko, Kanna Fujita, Seitaro Nomura, Yukari Uemura, Kenji Onoue, Momoko Hamano, Manami Katoh, Shintaro Yamada, Mikako Katagiri, Bo Zhang, Satoshi Hatsuse, Takanobu Yamada, Shunsuke Inoue, Masayuki Kubota, Kosuke Sawami, Tuolisi Heryed, Masamichi Ito, Eisuke Amiya, Masaru Hatano, Norifumi Takeda, Hiroyuki Morita, Yoshihiro Yamanishi, Yoshihiko Saito, Issei Komuro
Journal: JACC Heart Failure (2023)

Reliable predictors of treatment efficacy in heart failure have been long awaited. DNA damage has been implicated as a cause of heart failure. The purpose of this study was to investigate the association of DNA damage in myocardial tissue with treatment response and prognosis of heart failure. The authors performed immunostaining of DNA damage markers poly(ADP-ribose) (PAR) and γ-H2A.X in endomyocardial biopsy specimens from 175 patients with heart failure with reduced ejection fraction (HFrEF) of various underlying etiologies. They calculated the percentage of nuclei positive for each DNA damage marker (%PAR and %γ-H2A.X). The primary outcome was left ventricular reverse remodeling (LVRR) at 1 year, and the secondary outcome was a composite of cardiovascular death, heart transplantation, and ventricular assist device implantation. Patients who did not achieve LVRR after the optimization of medical therapies presented with significantly higher %PAR and %γ-H2A.X. The ROC analysis demonstrated good performance of both %PAR and %γ-H2A.X for predicting LVRR (AUCs: 0.867 and 0.855, respectively). There was a negative correlation between the mean proportion of DNA damage marker–positive nuclei and the probability of LVRR across different underlying diseases. In addition, patients with higher %PAR or %γ-H2A.X had more long-term clinical events (PAR HR: 1.63 [95% CI: 1.31-2.01; P < 0.001]; γ-H2A.X HR: 1.48 [95% CI: 1.27-1.72; P < 0.001]). DNA damage determines the consequences of human heart failure. Assessment of DNA damage is useful to predict treatment efficacy and prognosis of heart failure patients with various underlying etiologies.
Impact of Female Sex on Cardiogenic Shock Outcomes
Authors: Van-Khue Ton, Manreet K. Kanwar, Borui Li, Vanessa Blumer, Song Li, Elric Zweck, Shashank S. Sinha, Maryjane Farr, Shelley Hall, Rachna Kataria, Maya Guglin, Esther Vorovich, Jaime Hernandez-Montfort, A. Reshad Garan, Mohit Pahuja, Saraschandra Vallabhajosyula, Sandeep Nathan, Jacob Abraham, Neil M. Harwani, Gavin W. Hickey, Detlef Wencker, Andrew D. Schwartzman, Wissam Khalife, Claudius Mahr, Ju H. Kim, Arvind Bhimaraj, Paavni Sangal, Yijing Zhang, Karol D. Walec, Peter Zazzali, Daniel Burkhoff, Navin K. Kapur
Journal: JACC Heart Failure (2023)
Myeloid Cell Derived IL1β Contributes to Pulmonary Hypertension in HFpEF
Authors: Vineet Agrawal, Jonathan A. Kropski, Jason J. Gokey, Elizabeth Kobeck, Matthew B. Murphy, Katherine T. Murray, Niki L. Fortune, Christy S. Moore, David F. Meoli, Ken Monahan, Yan Ru Su, Thomas Blackwell, Deepak K. Gupta, Megha H. Talati, Santhi Gladson, Erica J. Carrier, James D. West, Anna R. Hemnes
Journal: Circulation Research (2023)

Pulmonary hypertension (PH) in heart failure with preserved ejection fraction (HFpEF) is a common and highly morbid syndrome, but mechanisms driving PH-HFpEF are poorly understood. We sought to determine whether a well-accepted murine model of HFpEF also displays features of PH, and we sought to identify pathways that might drive early remodeling of the pulmonary vasculature in HFpEF.
Abstract 16083: How Will the Use of New Heart Failure Treatments Impact US Health System Reimbursement Under Alternative Payment Models: Measuring the Impact of Sotagliflozin Use Among Patients Hospitalized for Heart Failure
Authors: Shanshan Wang, Jason Shafrin, Jaehong Kim, Slaven Sikirica, Alexander T Sandhu
Journal: Circulation (2023)

Background: In the SOLOIST-WHF clinical trial, sotagliflozin lowered rates of readmission and emergency department (ED) visits among patients hospitalized for worsening heart failure (HF), but its impact on health systems’ finances is unclear. Research Question: What is the economic impact of the adoption of sotagliflozin on health systems after incorporating reimbursement bonuses within alternative payment models (APM)? Goal: To quantify the financial impact on health systems of adopting sotagliflozin relative to standard of care (SoC) for treating patients with HF as in SOLOIST-WHF. Methods: This study created a decision tree model and estimated the clinical impact of sotagliflozin use relative to SoC from the SOLOIST-WHF trial. The model first assessed the impact of sotagliflozin on re-hospitalization, ED visit rates and mortality. Next, these clinical outcomes were translated into impacts on a health system’s finances relative to SoC within a one-year time frame under traditional fee-for-services (FFS) and three APMs: hospital readmissions reduction program (HRRP), Bundled Payments for Care Improvement (BPCI), and Accountable Care Organization (ACO). Results: An average community hospital (6,109 admissions annually) would have 83 patients per year with an index HF hospitalization. Sotagliflozin reduced the probability of re-hospitalization, ED visits, and deaths by 29.3%, 38.5%, and 17.8%, respectively vs. SoC. For hospitals not experiencing capacity constraint, sotagliflozin adoption increased financial returns by $9,365 per person (pp) ($781,340 per health system) under HRRP, $1,200 pp. ($100,106 per health system) for BPCI, and $1,078 pp. ($89,910 per health system) for ACO. (Figure 1) Conclusion: Sotagliflozin adoption decreased hospitalizations, ED visits, and deaths, which—under various APMs—led to a net positive financial impact on health systems after accounting for APM bonus payments. Sponsorship: Lexicon Pharmaceuticals, Inc.
Abstract 16904: Low-Dose Isoproterenol Administration in the Murine MDX Model Unmasks Progression of Duchenne-Associated Cardiomyopathy
Authors: Alyssa M Richards, Conner C Earl, Steven S Welc, Mark C Kowala, Larry W Markham, Craig J Goergen
Journal: Circulation (2023)

Introduction: The cardiovascular phenotype resulting from Duchenne muscular dystrophy (DMD) includes cardiomyopathy (CMP) leading to congestive heart failure and early mortality. CMP is the leading cause of death in DMD. Our objective was to characterize the progression of CMP in a murine model of DMD. We hypothesized that a genetic mouse model of DMD will exhibit significantly lower function over time as measured by ejection fraction when given an isoproterenol (IPT) challenge. Methods: We examined a mouse model of DMD from the Jackson Laboratory: C57BL/10ScSn- Dmd mdx /J (B10.mdx; n=6 female). The genetic group was paired with the wild type control strain C57BL/10ScSnJ (B10; n=6 female mice). B10.mdx (MDX) and B10 (WT) mice received intraperitoneal IPT administered via daily injections at 3 mg/kg. Cardiac function was assessed by 2D ultrasound using a Vevo3100 imaging system (FUJIFILM, VisualSonics) from the baseline, immediate effects of IPT injection at 1 minute, after 7, 14, and 21 days. Results: At 1 minute following the first IPT injection in WT and MDX, we observed increases in EF and HR for both groups ( Figure 1 ). While the changes in EF were notable yet not reaching significance, the differences within groups between baseline and 1 minute after injection were significant due to HR response ( p &lt;0.05).We observed decreases in EF for both groups between baseline and day 7 following IPT injections ( Figure 1 ). The changes in MDX EF between baseline and day 7 approached significance. The EF in both groups was maintained through day 7, day 14, and day 21. 2 deaths in MDX occurred during the treatment period and 1 death followed day 7. A WT sacrifice was made after day 14 due to severe dermatitis. Conclusion: Murine mdx models exhibit DMD-associated CMP comparable to humans. Associated humanlike phenotype includes decreased EF, FS, ESV, EDS, and SV. A low dose of IPT in MDW mice has the potential to unmask these changes within 7 days, reducing the need for longer term murine studies.
Abstract 13834: Prognosis of Patients With Atrial Fibrillation and Weight Loss: The Fushimi AF Registry
Authors: Moritake Iguchi, Yasuhiro Hamatani, Nobutoyo Masunaga, Mitsuru Ishii, Yuya Ide, Akiko Fujino, Takashi Yoshizawa, KOSUKE DOI, Syuhei Ikeda, Kenjiro Ishigami, Masahiro Esato, Hiromichi Wada, Koji Hasegawa, Hisashi Ogawa, Mitsuru Abe, Masaharu Akao
Journal: Circulation (2023)

Background: Atrial fibrillation (AF) is a common cardiac arrythmia in the elderly, in whom frailty is often a clinical issue. Weight loss is one of the key factors of frailty, and we previously reported that low body wight (≤50 kg) was associated with higher mortality and morbidity in patients with AF. However, the association of weight loss with prognosis of AF patients is unclear. Methods: The Fushimi AF registry is a community based prospective survey of AF patients in Japan. We collected data on body weight annually, and changes in body weight were obtained in 2,922 patients (mean age, 73 years; female 39.3%; mean body weight 59.8 kg). We defined weight loss as decrease in body weight ≥ 4.5 kg or 5% in the past year based on the frailty-defining criteria in the Cardiovascular Health Study. Results: During the follow-up, 1319 patients had weight loss (7.9% per person-year). Patients with weight loss were older, and had more hypertension, diabetes, coronary artery disease, chronic kidney disease, and heart failure at baseline than those without. Prevalence of prior stroke/systemic embolisms (SE) and major bleeding were similar between patients with and without weight loss. In the logistic regression analysis, hypertension, diabetes, chronic kidney disease, and heart failure were positively associated with development of weight loss, and incidence of stroke/SE was inversely associated with weight loss. Landmark analysis after the onset of weight loss revealed that patients with weight loss showed significantly higher incidence of all-cause death and cardiac death. Incidence of heart failure hospitalization, stroke/SE, and major bleeding were comparable between patients with and without weight loss. After adjustment for clinical confounders, weight loss was significantly associated with the incidence of all-cause death (hazard ratio, 1.79; 95% confidence interval, 1.54-2.09) and cardiac death (hazard ratio, 1.67; 95% confidence interval, 1.15-2.43). Subgroup analyses revealed that weight loss was also significantly associated with higher all-cause and cardiac mortality regardless of age, sex, and body weight at baseline. Conclusion: In AF patients, weight loss was significantly associated with higher all-cause and cardiac mortality.
Abstract 12506: Implantable Cardioverter Defibrillators for Primary Prevention in Patients With Ischemic and Non Ischemic Cardiomyopathy: A Meta-Analysis of 15 Randomized Controlled Trial
Authors: Vikash Jaiswal, Akash Jaiswal, Amira Mohamed Taha, Kriti Kalra, Yusra Nasir
Journal: Circulation (2023)

Background: The evidence to support implantable cardioverter defibrillator (ICD) in patients with ischemic and nonischemic cardiomyopathy for prevention of sudden cardiac death (SCD) is not robust, with conflicting results in randomized controlled trials. Objective: We aim to evaluate the impact of ICD therapy with conventional care for the primary prevention of death of various causes in adults with ischemic and nonischemic cardiomyopathy. Methods: We performed a systematic literature search on the electronic database for relevant articles from inception until 15th May 2022. Results: A total of 15 randomized controlled trials involving 9,999 patients: 9 (6523 patients) addressed ischemic cardiomyopathy, and 6 studies (3476 patients) reported nonischemic cardiomyopathy. The mean follow-up duration was 3.02 years. Pooled analysis showed that ICD therapy significantly reduced the risk of ACM (HR, 0.75(95%CI: 0.64-0.88), P&lt;0.001) from the control group. The magnitude of reduction was similar with ischemic (HR, 0.75(95%CI: 0.58-0.96), P=0.02), nonischemic (HR, 0.76(95%CI: 0.64-0.90), P&lt;0.01). There was 67% reduction in SCD among ICD therapy group (OR, 0.33(95%CI: 0.25-0.44), P&lt;0.00001) compared to the control, a similar trend was observed in both ischemic (OR, 0.39(95%CI: 0.28-0.56), P&lt;0.00001), and nonischemic cardiomyopathy (OR, 0.24(95%CI: 0.15-0.38), P&lt;0.00001). The ICD therapy group had a significant reduction of 65% reduction in arrhythmia-related death compared to control in ischemic cardiomyopathy (OR, 0.35(95%CI: 0.19-0.64), P&lt;0.001). However, there was a trend of 23% in cardiovascular mortality in the ICD group (OR, 0.77(95%CI: 0.58-1.02), P=0.07) but unable to reach statistical significance. Conclusion: Overall, primary prevention with ICD therapy reduced the incidence of all-cause mortality and sudden cardiac death among ischemic and nonischemic cardiomyopathy patients.
Abstract 19164: The Role of Klf6 in Hypertensive Inflammation
Authors: Alexandria P Haynes, Lale A Ertuglu, Ashley Pitzer Mutchler, Quanhu Sheng, Mohammad Saleem, Annet Kirabo
Journal: Circulation (2023)

Salt-sensitivity of blood pressure (SSBP) is a major risk factor for cardiovascular morbidity and mortality in people with or without hypertension. We previously found that oxidative lipid protein modification via NADPH oxidase in antigen presenting cells (APCs) contributes to SSBP but the underlying mechanisms are not known. HIF1α, which codes glycolytic enzymes in APCs enhances expression of Kruppel like factor 6 (KLF6), promoting expression of PDGFB which binds to the PDGFB receptor to activate NADPH oxidase, leading to increased oxidative stress and activation of mTOR. We hypothesize that HIF2α contributes to SSBP through activating NADPH oxidase by enhancing KLF6. To test this hypothesis, we isolated monocytes from human participants (N =11) and treated them with either high (190 mMol/L) or normal (150 mMol/L) Na+ in vitro for 72 hours and subsequently performed bulk RNA sequencing. We found that elevated sodium increases expression of HIFα (16437 ± 1810 vs. 42233 ± 6282, p = 2.28E-05) and KLF6 (9058 ± 584.3 vs. 12817 ± 1108, p = 0.6768). Interestingly, while the PDGFB receptor was upregulated by elevated sodium ( 21.18 ± 4.600 vs. 566.3 ± 205.3, p = 3.91E-13), the ligand PDGFB was downregulated (1249 ± 215.9 vs. 610.5 ± 118.2, p = 6.11E-04). In additional experiments, we performed single cell transcriptomic analysis in on immune cells of people phenotyped for SSBP. We found that in monocytes, as salt goes up with blood pressure so does the expression of KLF6 (r = 0.3773, p = 0.3561), PDGFB (r = 0.5604, p = 0.1485), and PDGFB receptor (r = 0.4436, p = 0.2709). Our data demonstrate the HIF1α-KLF6 pathway contributes to inflammation and SSBP.
Abstract 12563: Is Cardiometabolic Risk Reduction Sustainable in Routine Practice?
Authors: Jose Joel Hernandez Sevillano, Masih Babagoli, Pranav Mellacheruvu, Yitong Chen, Shelley Liu, Janet Johnson, Valentin Fuster, Jeffrey mechanick
Journal: Circulation (2023)

Introduction: Sustained cardiometabolic risk reduction is elusive in routine practice. Hypothesis: A multidisciplinary (endocrinology, cardiology, nutrition, diabetes technology/education, and exercise physiology) preventive cardiology center focused on the cardiometabolic-based chronic disease (CMBCD) model can exert long-term risk reduction in patients with and without cardiometabolic presentations. Methods: Yearly attainment of guideline-directed medical therapy targets of the metabolic driver at the most advanced stage in patients from the Center for Clinical Cardiovascular Health at Mount Sinai Heart with adiposity-, dysglycemia-, hypertension-, and lipid-based chronic disease with predisease, disease, or complications was measured. The main outcome was sustainability rate. Results: A total of 270 patients with a mean follow-up of 4.0±1.2 years were included. Sustainability, defined as target attainment in the year in question and in any other previous year(s), was observed in 93/127 (73%), 81/116 (70%), 55/80 (69%), 40/54 (74%), and 11/13 (85%) patients in years of engagement 2, 3, 4, 5, and 6, respectively. The median (interquartile range) number of years reaching the target for sustainers observed was: 2 (2-2); 3 (2-3); 3 (2-3.5); 4 (2-5); 5 (4-6) for patients with 2, 3, 4, 5, or 6 years of engagement at the Center. Conclusions: High sustainability rates for cardiometabolic risk reduction were observed in a multidisciplinary preventive cardiology center based on the CMBCD model with a focus on lifestyle medicine, in patients with and without cardiometabolic presentations.
Abstract 13830: Pheochromocytoma in a Patient With Tetralogy of Fallot and Chromosome 17p12 Duplication
Authors: Muskaan Aggarwal, Roy X Wang, Stephanie S Colello, Joshua M Saef, Sumeet Vaikunth
Journal: Circulation (2023)

Description of Case: A 22-year-old male with Tetralogy of Fallot (TOF) status post transannular patch repair, hypothyroidism, and known partial duplication of chromosome 17p12 concerning for Charcot-Marie-Tooth disease (CMT), presented to his cardiologist with exertional angina and dyspnea, difficulty gaining weight, and diaphoresis. Cardiac MRI demonstrated moderate to severe pulmonic regurgitation with regurgitation fraction of 35% and RV end-diastolic volume index of 150 cc/m 2 . He was referred for pulmonic valve replacement surgery. While awaiting surgical evaluation, he presented to an ER with new hypertension with blood pressure to 240/140 and tachycardia to 107. A CT scan demonstrated a 4.3 x 5.0 x 4.4 cm mass in the right adrenal gland. On admission he was started on phenoxybenzamine and carvedilol. Workup revealed elevated catecholamines and metanephrines ( Table ). He underwent surgical adrenalectomy without complications. Immunohistochemical staining was consistent with pheochromocytoma. Post-procedurally, he was normotensive off medications. He was seen in clinic three weeks after surgery with significant improvement in symptoms. Discussion: We report on a novel genetic association of chromosome 17p12 duplication and pheochromocytoma. The region transcribes peripheral myelin protein-22, which has associations with CMT. Overlap has been demonstrated in other CMT-associated mutations and pheochromocytoma syndromes (e.g. kinesin family member 1B). In congenital heart disease, risk for pheochromocytoma is felt to be driven by hypoxia causing catecholamine secretion, adrenal hyperplasia, and eventual neoplasia. Further study is needed to characterize genetic associations between pheochromocytoma, neuropathy, and congenital heart disease. This patient’s presentation is a lesson in maintaining a high index of suspicion for pheochromocytoma in congenital heart disease, especially with associated genetic syndromes.
Abstract 16913: The Association Between Adverse Childhood Experiences and Physiologic Age as Determined by Artificial Intelligence-ECG
Authors: Betsy J Medina-Inojosa, Jose R Medina-Inojosa, zhuo chen, Matthew Clark, Kathryn Mangold, Nazanin Rajai, Amir Lerman, Zachi Attia, Paul Friedman, Francisco Lopez-Jimenez
Journal: Circulation (2023)

Background: The gap between electrocardiogram (ECG) artificial intelligence-derived age (ECG-Age) and chronological age (Age-Gap) predicts cardiovascular (CV) comorbidities and mortality reflecting physiologic age. Adverse childhood experiences (ACEs) are traumatic and harmful events that impact adulthood CV outcomes. We hypothesized that ACEs would be associated with physiologic age as determined by the Age-Gap. Methods: We applied a previously validated ECG-Age algorithm to the ECGs of 1,988 consecutive individuals aged ≥18, that within 2 years completed an ACEs questionnaire as part of psychological evaluations for weight management. The ACE questionnaire assesses 3 psychosocial domains (i) childhood abuse (psychological, physical or sexual), (ii) household dysfunction (substance abuse, mental illness, female figure treated violently, criminal behavior and parental separation/divorce) and (iii) neglect (emotional or physical) before age 18; results ranged 0 to 10 and were categorized as burden (0, 1-3, and ≥4) and presence (abuse, household dysfunction, neglect). Age-Gap was operationalized as (≤mean or &gt; mean) positive values reflect physiological aging. Logistic regression analyses tested the association between ACE and Age-Gap. Results: Mean ± SD chronological age was 49±13 yr, ECG-Age 54±12 yr, Age-Gap 4.26±8.95 yr,75% women, average ACE 2±2, 32% experienced 0, 44% 1-3, and 24% ≥4 ACEs. Age-Gap was 1.4 years higher in those who experienced at least 1 ACE. Compared to those who didn’t experience ACE those who faced 1-3 ACE were more likely to have an Age-Gap &gt;mean (OR 1.28 95%CI 1.57-1.04) independent of sex and the age-adjusted Charlson comorbidity index Fig A. Also, they were more prone to experiencing neglect and household dysfunction Fig B. Conclusions: Age-gap was associated with ACEs burden and domains, underscoring the need to identify ACEs during clinical evaluations to prevent ACEs at the individual, family, and community levels.
Abstract 12535: Spontaneous Coronary Artery Dissection in Women: A New Role for Autoimmunity?
Authors: Giovanni Civieri, Giulia Masiero, Marta Vadori, Laura Iop, valeria pergola, Emanuele Cozzi, Sabino Iliceto, Francesco Tona
Journal: Circulation (2023)

Introduction: Spontaneous coronary artery dissection (SCAD) is an uncommon cause of myocardial infarction (MI) in women, with a still unclear pathophysiology. Autoantibodies targeting angiotensin-II receptor type 1 (AT1R) and endothelin-1 receptor type A (ETAR) (AT1R-AAs and ETAR-AAs, respectively) lead to endothelial dysfunction and have already been associated with aortic dissection. Hypothesis: We hypothesized that titers of AT1R-AAs and ETAR-AAs are higher in patients with SCAD compared to controls. Methods: Our case-control study was conducted at Padua University Hospital between January 2022 and June 2022. Female patients diagnosed at coronary angiography with MI and SCAD were consecutively enrolled. Ten women with SCAD and 20 age-matched controls (10 women with ST-elevation MI (STEMI) and 10 healthy women) were included. Serum levels for AT1R-AAs and ETAR-AAs were determined for each participant. Absolute autoantibody titers and seropositivity prevalence were compared between SCAD patients, STEMI patients, and healthy women. Seropositivity was defined according to the threshold value suggested by the manufacturer (&gt;10 U/mL). Results: Six out of 10 (60%) women with MI and SCAD were seropositive for AT1R-AAs and ETAR-AAs. In contrast, only one (10%) healthy woman and one (10%) STEMI patient were seropositive for AT1R-AAs (p=0.03 and p=0.03, respectively). One STEMI patient was seropositive for ETAR-AAs, while none of the healthy women was found to be seropositive (p=0.03 and p=0.01, respectively). The median autoantibody titer was significantly higher in SCAD patients than in healthy women (p=0.01 for AT1R-AAs; p=0.02 for ETAR-AAs) and STEMI patients (p&lt;0.001 for AT1R-AAs; p=0.002 for ETAR-AAs). Conclusions: AT1R-AAs and ETAR-AAs seropositivity is significantly higher in SCAD women than in healthy women or female patients with STEMI. Our findings suggest a possible role for AT1R-AAs and ETAR-AAs in the pathophysiology of SCAD in women with MI.